Human leukocyte antigen (HLA) is the most polymorphic gene in the human genome. Knowledge about HLA polymorphism in relation to possible peptide-based, T cell-restricted vaccination protocols is important for understanding the physiology of T cell recognition and for improving strategies of T cell antigen-specific vaccination. During the past year the HLA laboratory developed techniques for high-resolution typing of HLA classes I and II, using polymerase chain reaction techniques. Furthermore, a technique was developed for the analysis of HLA-A2 subtypes (the dominant allele in the U.S. population). We also defined models to study the heterogeneity of expression of HLA class I molecules in different tissues and described mechanisms by which some tissues may escape immune recognition simply by losing or downregulating the expression of HLA molecules. In the future we will explore techniques aimed at exemplifying the relevance of the polymorphism of HLA with regard to T cell activation and inactivation. With this purpose in mind, new techniques are being developed aimed at screening HLA and T cell receptor polymorphisms by heteroduplex analysis, automatized sequencing, and surface plasmon resonance. The ultimate goal is to identify the steps occurring in response to T antigen-specific vaccination and their correlation with clinical responses.